• 四川大學華西醫(yī)院呼吸內(nèi)科(四川成都 610041);

目的 觀察阿魏酸鈉對肺纖維化大鼠肺組織轉(zhuǎn)化生長因子β1(TGF-β1)信號通路分子mRNA表達的影響,探討其防治肺纖維化的作用及機制。方法 氣管內(nèi)滴入博來霉素(5 mg/kg)建立大鼠肺纖維化模型。將30只SD大鼠隨機分為三組(每組10只):對照組、肺纖維化模型組和阿魏酸鈉組。HE染色檢測肺組織病理改變,膠原纖維染色檢測膠原纖維表達,原位雜交技術(shù)檢測肺組織TGF-βRⅡ及Smad4 mRNA表達,實時熒光定量RT-PCR技術(shù)檢測TGF-β1 mRNA表達。結(jié)果 膠原纖維染色顯示模型組大鼠肺內(nèi)膠原纖維表達顯著高于對照組和阿魏酸鈉組(P lt;0.001)。大鼠肺內(nèi)TGF-β1、TGF-βRⅡ和Smad4的mRNA表達在模型組顯著高于對照組(P lt;0.01),在阿魏酸鈉組顯著低于模型組(P lt;0.05)。結(jié)論 阿魏酸鈉能有效地減輕肺纖維化大鼠肺組織的纖維化程度,其作用機制主要是通過抑制TGF-β1、TGF-βRⅡ和Smad4的mRNA表達上調(diào),從而干擾TGF-β1/Smad4信號通路對靶基因的激活來實現(xiàn)的。

引用本文: 穆茂,程德云,楊禮騰,方詢,聶莉,胡小波. 阿魏酸鈉對肺纖維化大鼠肺組織轉(zhuǎn)化生長因子β1信號通路分子mRNA表達的影響. 中國呼吸與危重監(jiān)護雜志, 2007, 6(2): 110-113. doi: 復(fù)制

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1. Xaubet A,Marin-Arguedas A,Lario S,et al.Transforming growth factor-beta1 gene polymorphisms are associated with disease progression in idiopathic pulmonary fibrosis.Am J Respir Crit Care Med,2003,168:410-411.
2. 賀德,曾志良,曹建華,等.阿魏酸鈉抗大鼠肝纖維化.世界華人消化雜志,2002,10:240-241.
3. 陳輝珍,樊均明.阿魏酸鈉與腎間質(zhì)纖維化關(guān)系的探討.中藥新藥與臨床藥理,2003,14:353-355.
4. 王伯沄,李玉松,黃高異,主編.病理學技術(shù).北京:人民衛(wèi)生出版社,2000:142-144.
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6. Clark JG,Kostal KM,Marino BA.Bleomycin-induced pulmonary fibrosis in hamsters.An alveolar macrophage product increases fibroblast prostaglandin E2 and cyclic adenosine monophosphate and suppresses fibroblast proliferation and collagen production.J Clin Invest,1983,72:2082-2091.
7. 徐鈺,高占成,陳彬,等.γ-干擾素轉(zhuǎn)基因表達對不同時期博萊霉素致小鼠肺間質(zhì)纖維化的作用.中國呼吸與危重監(jiān)護雜志,2005,4:130-134.
8. 馬躍文,侯顯明,康健,等.轉(zhuǎn)化生長因子β1及其Ⅰ、Ⅱ型受體在肺纖維化組織中的表達變化和意義.中華結(jié)核和呼吸雜志,2000,23:701-702.
9. 徐曉峰,王辰,代華平,等.大鼠肺纖維化過程中轉(zhuǎn)化生長因子β1及其受體的同相表達.中華結(jié)核和呼吸雜志,2002,25:550-551.
10. 劉濤,宋良文.肺纖維化發(fā)生的分子機制和早期防治研究進展.軍事醫(yī)學科學院院刊,2003,27:312-316.
11. Xaubet A,Marin-Arguedas A,Lario S,et al.Transforming growth factor-beta1 gene polymorphisms are associated with disease progression in idiopathic pulmonary fibrosis.Am J Respir Crit Care Med,2003,168:431-435.
12. Bartram U,Speer CP.The role of transforming growth factor beta in lung development and disease.Chest,2004,125:754-765.
13. Wrana JL,Attisano L,Wieser R,et al.Mechanism of activation of the TGF-beta receptor.Nature,1994,370:341-347.
14. Heldin CH,Miyazono K,ten Dijke P.TGF-β signaling from cell membrane to nucleus through SMAD proteins.Nature,1997,390:465-471.
15. Correia JJ,Chacko BM,Lam SS,et al.Sedimentation studies reveal a direct role of phosphorylation in Smad3:Smad4 homo- and hetero-trimerization.Biochemistry,2001,40:1473-1482.
16. 廖丹,江建寧.肝纖維化形成的機制——信號轉(zhuǎn)導通路TGF-β/Smad的作用概論.國外醫(yī)學(流行病學與傳染病學分冊),2004,31:170-172.
17. Zhang W,Ou J,Inagaki Y,et al.Synergistic cooperation between Spl and Smad3/Smad4 mediates transforming growth factor betal stimulation of alpha2(I)-collagen (COLIA2) transcription.J Biol Chem,2000,275:39237-39245.
18. Ghosh AK,Yuan W,Mori Y,et al.Antagonistic regulation of type I collagen gene expression by interferon-gamma and transforming growth facter-beta.Integration at the level of p300/CBP transcriptional coactivators.J Biol Chem,2001,276:11041-11048.
19. 劉向峰,李娜.阿魏酸鈉的臨床應(yīng)用.寧夏醫(yī)學雜志,2005,27:69-70.
20. 黃瑾,胡晉紅,邱磊,等.阿魏酸鈉抑制肝星狀細胞合成膠原的機制.藥學學報,2004,39:577 -580.
  1. 1. Xaubet A,Marin-Arguedas A,Lario S,et al.Transforming growth factor-beta1 gene polymorphisms are associated with disease progression in idiopathic pulmonary fibrosis.Am J Respir Crit Care Med,2003,168:410-411.
  2. 2. 賀德,曾志良,曹建華,等.阿魏酸鈉抗大鼠肝纖維化.世界華人消化雜志,2002,10:240-241.
  3. 3. 陳輝珍,樊均明.阿魏酸鈉與腎間質(zhì)纖維化關(guān)系的探討.中藥新藥與臨床藥理,2003,14:353-355.
  4. 4. 王伯沄,李玉松,黃高異,主編.病理學技術(shù).北京:人民衛(wèi)生出版社,2000:142-144.
  5. 5. Weller SA.,Elphinstone JG,Smith NC,et al.Detection of Ralstonia solanacearum strains with a quantitative,multiplex,real-time,fluorogenic PCR (TaqMan) assay.Appl Environ Microbiol,2000,66:2853-2858.
  6. 6. Clark JG,Kostal KM,Marino BA.Bleomycin-induced pulmonary fibrosis in hamsters.An alveolar macrophage product increases fibroblast prostaglandin E2 and cyclic adenosine monophosphate and suppresses fibroblast proliferation and collagen production.J Clin Invest,1983,72:2082-2091.
  7. 7. 徐鈺,高占成,陳彬,等.γ-干擾素轉(zhuǎn)基因表達對不同時期博萊霉素致小鼠肺間質(zhì)纖維化的作用.中國呼吸與危重監(jiān)護雜志,2005,4:130-134.
  8. 8. 馬躍文,侯顯明,康健,等.轉(zhuǎn)化生長因子β1及其Ⅰ、Ⅱ型受體在肺纖維化組織中的表達變化和意義.中華結(jié)核和呼吸雜志,2000,23:701-702.
  9. 9. 徐曉峰,王辰,代華平,等.大鼠肺纖維化過程中轉(zhuǎn)化生長因子β1及其受體的同相表達.中華結(jié)核和呼吸雜志,2002,25:550-551.
  10. 10. 劉濤,宋良文.肺纖維化發(fā)生的分子機制和早期防治研究進展.軍事醫(yī)學科學院院刊,2003,27:312-316.
  11. 11. Xaubet A,Marin-Arguedas A,Lario S,et al.Transforming growth factor-beta1 gene polymorphisms are associated with disease progression in idiopathic pulmonary fibrosis.Am J Respir Crit Care Med,2003,168:431-435.
  12. 12. Bartram U,Speer CP.The role of transforming growth factor beta in lung development and disease.Chest,2004,125:754-765.
  13. 13. Wrana JL,Attisano L,Wieser R,et al.Mechanism of activation of the TGF-beta receptor.Nature,1994,370:341-347.
  14. 14. Heldin CH,Miyazono K,ten Dijke P.TGF-β signaling from cell membrane to nucleus through SMAD proteins.Nature,1997,390:465-471.
  15. 15. Correia JJ,Chacko BM,Lam SS,et al.Sedimentation studies reveal a direct role of phosphorylation in Smad3:Smad4 homo- and hetero-trimerization.Biochemistry,2001,40:1473-1482.
  16. 16. 廖丹,江建寧.肝纖維化形成的機制——信號轉(zhuǎn)導通路TGF-β/Smad的作用概論.國外醫(yī)學(流行病學與傳染病學分冊),2004,31:170-172.
  17. 17. Zhang W,Ou J,Inagaki Y,et al.Synergistic cooperation between Spl and Smad3/Smad4 mediates transforming growth factor betal stimulation of alpha2(I)-collagen (COLIA2) transcription.J Biol Chem,2000,275:39237-39245.
  18. 18. Ghosh AK,Yuan W,Mori Y,et al.Antagonistic regulation of type I collagen gene expression by interferon-gamma and transforming growth facter-beta.Integration at the level of p300/CBP transcriptional coactivators.J Biol Chem,2001,276:11041-11048.
  19. 19. 劉向峰,李娜.阿魏酸鈉的臨床應(yīng)用.寧夏醫(yī)學雜志,2005,27:69-70.
  20. 20. 黃瑾,胡晉紅,邱磊,等.阿魏酸鈉抑制肝星狀細胞合成膠原的機制.藥學學報,2004,39:577 -580.